Regulation of aortic wall structure by the renin-angiotensin system in Wistar rats.
The effects of long-term angiotensin-converting enzyme (ACE) inhibition, angiotensin II (AT1)-receptor blockade, calcium-entry blockade, or cyclosporin A treatment on rat aortic wall structure were investigated to determine the role of the renin-angiotensin system in the physiologic regulation of vascular structure in vivo. Groups of 15 Wistar rats were treated for 6 weeks either with the ACE inhibitors lisinopril or fosinopril or with the AT1-antagonists D 8731 or losartan (each 10 mg/kg/day) or with the calcium antagonist isradipine, 60 mg/kg/day, or cyclosporin A, 15 mg/kg/day, or a combination of cyclosporin with one of the vasodilators. Media thickness, vascular smooth-muscle cell density, and intima thickening were measured in histologic sections of the abdominal aorta. In addition, aortic contractility and heart weight were determined. Long-term ACE inhibition, AT1-receptor blockade, and calcium-entry blockade reduced aortic media thickness and increased media smooth-muscle cell density. Only ACE inhibition significantly reduced the extent of intima lesions. Media thickness correlated well with the maximal aortic contraction to phenylephrine and serotonin but not to angiotensin II. ACE inhibition and AT1-receptor blockade decreased heart weight, whereas calcium antagonism increased it. Cyclosporin treatment was without effect on any of these parameters. The data demonstrate a significant long-term influence of the renin-angiotensin system on aortic wall structure and function in Wistar rats.
Unkelbach
M
M
Department of Internal Medicine/Cardiology, German Heart Institute and Virchow-Klinikum, Humboldt University, Berlin.
Auch-Schwelk
W
W
Unkelbach
E
E
Jautzke
G
G
Fleck
E
E
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D017539:Tunica Intima / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D018501:Antirheumatic Agents; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D016572:Cyclosporine